Search

Percutaneous coronary interventions (PCI) in calcified coronary artery lesions are associated with impaired stent expansion, higher rate of periprocedural complications and cardiac mortality. Lesion preparation using calcium modifying techniques such as Rotational Atherectomy (RA) or Intravascular Lithotripsy (IVL) has been advocated. Studies comparing these technologies are lacking. We aimed to compare in-stent pressure gradients, evaluated by vessel fractional flow reserve (vFFR), in calcific lesions treated using either RA or IVL.Patients undergoing either RA- or IVL-assisted PCI from two European centers were included. Propensity score matching (1:2) was performed to control for potential bias. Primary outcome was post-PCI in-stent pressure gradients calculated by vFFR (vFFRgrad). Secondary outcomes included the proportion of patients with complete functional revascularization defined as distal vFFR post-PCI (vFFRpost) ≥ 0.90.From a cohort of 210 patients, 105 matched patients (70 RA and 35 IVL) were included. Pre-PCI vFFR did not differ between groups (0.65 ± 0.13 RA and 0.67 ± 0.11 IVL). After PCI, in-stent pressure gradients were significantly lower in the IVL group (0.032 ± 0.026 vs 0.043 ± 0.026 in the RA group, p = 0.024). The proportions of vessels with functional complete revascularization was similar between the two groups (32.9% vs. 37.1% in the RA and IVL group, respectively; p = 0.669).Calcific lesions preparation with IVL is effective and resulted in lower in-stent pressure gradients compared to RA. Approximately one third of the patients undergoing PCI for a severely calcified lesion achieved functional revascularization with no difference between rotational RA and IVL.

Aims: Prior percutaneous coronary intervention (PCI) is increasingly encountered in acute coronary syndrome (ACS) patients, with uncertain significance. We sought to evaluate the impact of prior PCI in ACS patients. Methods and results: Patients with ACS enrolled in the prospective PROSPECT registry underwent three-vessel intravascular ultrasound and virtual histology evaluation after successful PCI of the culprit lesion(s). We identified patients with prior PCI (>6 months before index ACS) and compared their outcomes to those without prior PCI. Time-to-event for major adverse cardiac events (MACE) was estimated up to three years, and the independent association between prior PCI and MACE was evaluated in a multivariable model. Among 696 patients enrolled, 77 (11.1%) had prior PCI. They were older and more likely to have prior myocardial infarction, chronic kidney disease, and congestive heart failure. At three years, patients with prior PCI had significantly higher rates of cardiac death, rehospitalisation for worsening angina, and MACE (adjusted HR=1.73 [95% CI: 1.09, 2.75], p=0.02), independent of other comorbidities and intravascular ultrasound findings. Conclusions: Prior PCI was noted in over 10% of patients with ACS and was associated with higher mortality and morbidity, independent of other comorbidities. Prior PCI should be considered a high-risk feature when evaluating ACS patients.

Background: we hypothesized that fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) would be superior to medical therapy as initial treatment in patients with stable coronary artery disease.Methods: among 1220 patients with angiographically significant stenoses, those in whom at least one stenosis was hemodynamically significant (FFR, ≤0.80) were randomly assigned to FFR-guided PCI plus medical therapy or to medical therapy alone. Patients in whom all stenoses had an FFR of more than 0.80 received medical therapy and were entered into a registry. The primary end point was a composite of death, myocardial infarction, or urgent revascularization.Results: a total of 888 patients underwent randomization (447 patients in the PCI group and 441 in the medical-therapy group). At 5 years, the rate of the primary end point was lower in the PCI group than in the medical-therapy group (13.9% vs. 27.0%; hazard ratio, 0.46; 95% confidence interval [CI], 0.34 to 0.63; PConclusions: in patients with stable coronary artery disease, an initial FFR-guided PCI strategy was associated with a significantly lower rate of the primary composite end point of death, myocardial infarction, or urgent revascularization at 5 years than medical therapy alone. Patients without hemodynamically significant stenoses had a favorable long-term outcome with medical therapy alone. (Funded by St. Jude Medical and others; FAME 2 ClinicalTrials.gov number, NCT01132495 .).

Background Pressure measurement for the duration of the wave-free period (WFP) is considered essential for resting-state physiological assessment of coronary stenosis severity using the instantaneous wave-free ratio (iFR). Objectives The aim of this study was to compare other diastolic resting indexes to iFR. Methods In the population of the VERIFY2 (Pd/Pa vs iFR in an Unselected Population Referred for Invasive Angiography) study, iFR calculated by proprietary software (Volcano Harvest, Volcano Corporation, Rancho Cordova, California) was compared with the ratio of resting distal coronary pressure and aortic pressure during the complete duration of diastole (dPR), 25% to 75% of diastole (dPR25–75), and midpoint of diastole (dPRmid), along with Matlab calculated iFR (iFRmatlab) and iFR-like indexes shortening the length of the WFP by 50 and 100 ms (iFR−50ms and iFR−100ms), respectively. Mutual differences, Spearman correlations, area under the curve values from receiver-operating characteristic analyses, and diagnostic performance with respect to iFR and fractional flow reserve (FFR) were calculated for all indexes. Results Median iFR in 197 patients with 257 vessels was 0.91 with an interquartile range of 0.87 to 0.95. The mutual differences (± SD) with iFR were 0.006 ± 0.011 (dPR), 0.001 ± 0.007 (dPR25–75), 0.001 ± 0.008 (dPRmid), 0.005 ± 0.009 (iFRmatlab), 0.003 ± 0.008 (iFR−50ms), and 0.001 ± 0.009 (iFR−100ms). Correlations for all indexes with iFR were >0.99 (p < 0.001 for all). Area under the curve values for predicting iFR were >0.99 for all indexes as well. Diagnostic accuracy compared with FFR was 76% to 77% for all indexes including iFR. Conclusions All diastolic resting indexes tested were identical to iFR, both numerically and with respect to their agreement with FFR. A numerically equal value to iFR can be determined without restriction to the WFP. Cutoff values, guidelines, and clinical recommendations for iFR can therefore be extended to these other indexes. (Pd/Pa vs iFR in an Unselected Population Referred for Invasive Angiography [VERIFY2]; NCT02377310)

BACKGROUND: Patients with obstructive left main coronary artery disease are usually treated with coronary-artery bypass grafting (CABG). Randomized trials have suggested that drug-eluting stents may be an acceptable alternative to CABG in selected patients with left main coronary disease. METHODS: We randomly assigned 1905 eligible patients with left main coronary artery disease of low or intermediate anatomical complexity to undergo either percutaneous coronary intervention (PCI) with fluoropolymer-based cobalt-chromium everolimus-eluting stents (PCI group, 948 patients) or CABG (CABG group, 957 patients). Anatomic complexity was assessed at the sites and defined by a Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score of 32 or lower (the SYNTAX score reflects a comprehensive angiographic assessment of the coronary vasculature, with 0 as the lowest score and higher scores [no upper limit] indicating more complex coronary anatomy). The primary end point was the rate of a composite of death from any cause, stroke, or myocardial infarction at 3 years, and the trial was powered for noninferiority testing of the primary end point (noninferiority margin, 4.2 percentage points). Major secondary end points included the rate of a composite of death from any cause, stroke, or myocardial infarction at 30 days and the rate of a composite of death, stroke, myocardial infarction, or ischemia-driven revascularization at 3 years. Event rates were based on Kaplan-Meier estimates in time-to-first-event analyses. RESULTS: At 3 years, a primary end-point event had occurred in 15.4% of the patients in the PCI group and in 14.7% of the patients in the CABG group (difference, 0.7 percentage points; upper 97.5% confidence limit, 4.0 percentage points; P=0.02 for noninferiority; hazard ratio, 1.00; 95% confidence interval, 0.79 to 1.26; P=0.98 for superiority). The secondary end-point event of death, stroke, or myocardial infarction at 30 days occurred in 4.9% of the patients in the PCI group and in 7.9% in the CABG group (P

Background— The Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME) 2 trial demonstrated a significant reduction in subsequent coronary revascularization among patients with stable angina and at least 1 coronary lesion with a fractional flow reserve ≤0.80 who were randomized to percutaneous coronary intervention (PCI) compared with best medical therapy. The economic and quality-of-life implications of PCI in the setting of an abnormal fractional flow reserve are unknown. Methods and Results— We calculated the cost of the index hospitalization based on initial resource use and follow-up costs based on Medicare reimbursements. We assessed patient utility using the EQ-5D health survey with US weights at baseline and 1 month and projected quality-adjusted life-years assuming a linear decline over 3 years in the 1-month utility improvements. We calculated the incremental cost-effectiveness ratio based on cumulative costs over 12 months. Initial costs were significantly higher for PCI in the setting of an abnormal fractional flow reserve than with medical therapy ($9927 versus $3900, P P P Conclusions— PCI of coronary lesions with reduced fractional flow reserve improves outcomes and appears economically attractive compared with best medical therapy among patients with stable angina. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01132495.

Objective: We propose a novel technique called pressure-bounded coronary flow reserve (pb-CFR) and demonstrate its application to the randomized DEFER trial. Background: Intracoronary flow reserve assessment remains underutilized relative to pressure measurements partly due to less robust tools. Methods: While rest and hyperemic intracoronary pressure measurements cannot quantify CFR exactly, they do provide upper and lower bounds. We validated pb-CFR invasively against traditional CFR, then applied it to high fractional flow reserve (FFR ≥ 0.75) lesions in DEFER randomized to revascularization or medical therapy. Results: pb-CFR showed an 84.4% accuracy to predict invasive CFR < 2 or CFR ≥ 2 in 107 lesions. In its proof of concept application to DEFER lesions with FFR ≥ 0.75, the 28 with pb-CFR < 2 compared to 28 with pb-CFR ≥ 2 had a non-significant reduction in freedom from angina (61% vs. 71% at 5 years, P = 0.57) and a non-significantly higher rate of major adverse cardiac events (MACE, 25% vs. 15%, P = 0.34). Lesions with FFR ≥ 0.75 but pb-CFR < 2 showed no difference in freedom from angina (61% vs. 50%, P = 0.54) or MACE (25% vs. 38%, P = 0.27) between the 28 randomized to medical therapy and the 16 randomized to revascularization. Conclusions: pb-CFR offers a new method for studying FFR/CFR discordances using regular pressure wire measurements. As an example application, DEFER suggested that low pb-CFR with high FFR may be a risk marker for more angina and worse outcomes, but that this risk cannot be modified by revascularization.

International audience; BACKGROUND: We hypothesized that in patients with stable coronary artery disease and stenosis, percutaneous coronary intervention (PCI) performed on the basis of the fractional flow reserve (FFR) would be superior to medical therapy. METHODS: In 1220 patients with stable coronary artery disease, we assessed the FFR in all stenoses that were visible on angiography. Patients who had at least one stenosis with an FFR of 0.80 or less were randomly assigned to undergo FFR-guided PCI plus medical therapy or to receive medical therapy alone. Patients in whom all stenoses had an FFR of more than 0.80 received medical therapy alone and were included in a registry. The primary end point was a composite of death from any cause, nonfatal myocardial infarction, or urgent revascularization within 2 years. RESULTS: The rate of the primary end point was significantly lower in the PCI group than in the medical-therapy group (8.1% vs. 19.5%; hazard ratio, 0.39; 95% confidence interval [CI], 0.26 to 0.57; P\textless0.001). This reduction was driven by a lower rate of urgent revascularization in the PCI group (4.0% vs. 16.3%; hazard ratio, 0.23; 95% CI, 0.14 to 0.38; P\textless0.001), with no significant between-group differences in the rates of death and myocardial infarction. Urgent revascularizations that were triggered by myocardial infarction or ischemic changes on electrocardiography were less frequent in the PCI group (3.4% vs. 7.0%, P=0.01). In a landmark analysis, the rate of death or myocardial infarction from 8 days to 2 years was lower in the PCI group than in the medical-therapy group (4.6% vs. 8.0%, P=0.04). Among registry patients, the rate of the primary end point was 9.0% at 2 years. CONCLUSIONS: In patients with stable coronary artery disease, FFR-guided PCI, as compared with medical therapy alone, improved the outcome. Patients without ischemia had a favorable outcome with medical therapy alone. (Funded by St. Jude Medical; FAME 2 ClinicalTrials.gov number, NCT01132495.).

We thank Drs Fan and He for their interest in our article.1 They raise a number of issues that have both philosophical and technical dimensions. We agree that patients may vary in the degree to which their symptoms reduce quality of life, and that an individual may be more (or less) willing to have a procedure to relieve angina. Although individuals do vary in their preferences, the average in preferences in the target population is still the best metric to evaluate procedures that apply to populations. Our analysis was performed …

BACKGROUND: Fractional flow reserve (FFR) has become an established tool for guiding treatment, but its graded relationship to clinical outcomes as modulated by medical therapy versus revascularization remains unclear.OBJECTIVES: The study hypothesized that FFR displays a continuous relationship between its numeric value and prognosis, such that lower FFR values confer a higher risk and therefore receive larger absolute benefits from revascularization.METHODS: Meta-analysis of study- and patient-level data investigated prognosis after FFR measurement. An interaction term between FFR and revascularization status allowed for an outcomes-based threshold.RESULTS: A total of 9,173 (study-level) and 6,961 (patient-level) lesions were included with a median follow-up of 16 and 14 months, respectively. Clinical events increased as FFR decreased, and revascularization showed larger net benefit for lower baseline FFR values. Outcomes-derived FFR thresholds generally occurred around the range 0.75 to 0.80, although limited due to confounding by indication. FFR measured immediately after stenting also showed an inverse relationship with prognosis (hazard ratio: 0.86, 95% confidence interval: 0.80 to 0.93; p < 0.001). An FFR-assisted strategy led to revascularization roughly half as often as an anatomy-based strategy, but with 20% fewer adverse events and 10% better angina relief.CONCLUSIONS: FFR demonstrates a continuous and independent relationship with subsequent outcomes, modulated by medical therapy versus revascularization. Lesions with lower FFR values receive larger absolute benefits from revascularization. Measurement of FFR immediately after stenting also shows an inverse gradient of risk, likely from residual diffuse disease. An FFR-guided revascularization strategy significantly reduces events and increases freedom from angina with fewer procedures than an anatomy-based strategy.

International audience; BACKGROUND: Coronary computed tomographic angiography (CTA) plus estimation of fractional flow reserve using CTA (FFRCT) safely and effectively guides initial care over 90 days in patients with stable chest pain. Longer-term outcomes are unknown. OBJECTIVES: The study sought to determine the 1-year clinical, economic, and quality-of-life (QOL) outcomes of using FFRCT instead of usual care. METHODS: Consecutive patients with stable, new onset chest pain were managed by either usual testing (n = 287) or CTA (n = 297) with selective FFRCT (submitted in 201, analyzed in 177); 581 of 584 (99.5%) completed 1-year follow-up. Endpoints were adjudicated major adverse cardiac events (MACE) (death, myocardial infarction, unplanned revascularization), total medical costs, and QOL. RESULTS: Patients averaged 61 years of age with a mean 49% pre-test probability of coronary artery disease. At 1 year, MACE events were infrequent, with 2 in each arm of the planned invasive group and 1 in the planned noninvasive cohort (usual care strategy). In the planned invasive stratum, mean costs were 33% lower with CTA and selective FFRCT (\8,127 vs. \12,145 usual care; p \textless 0.0001); in the planned noninvasive stratum, mean costs did not differ when using an FFRCT cost weight of zero (\3,049 FFRCT vs. \2,579; p = 0.82), but were higher when using an FFRCT cost weight equal to CTA. QOL scores improved overall at 1 year (p \textless 0.001), with similar improvements in both groups, apart from the 5-item EuroQOL scale scores in the noninvasive stratum (mean change of 0.12 for FFRCT vs. 0.07 for usual care; p = 0.02). CONCLUSIONS: In patients with stable chest pain and planned invasive coronary angiography, care guided by CTA and selective FFRCT was associated with equivalent clinical outcomes and QOL, and lower costs, compared with usual care over 1-year follow-up. (The PLATFORM Study: Prospective LongitudinAl Trial of FFRct: Outcome and Resource IMpacts [PLATFORM]; NCT01943903).

To compare the effective radiation dose (ERD) needed to obtain information on coronary anatomy and physiology by a non-invasive versus an invasive diagnostic strategy.Knowledge of anatomy and physiology is needed for management of patients with coronary artery disease (CAD). There is, however, a growing concern about detrimental long-term effects of radiation associated with diagnostic procedures.In a total of 671 patients with suspected CAD, we compared the ERD needed to obtain anatomical and physiological information through a non-invasive strategy or an invasive strategy. The non-invasive strategy consisted of coronary computed tomography angiography (CCTA) and single photon emission computed tomography (SPECT). The invasive strategy included coronary angiography (CA) and fractional flow reserve (FFR) measurement. In 464 patients, the data were acquired in Period 2009 and in 207 the data were acquired in Period 2011 (after each period, the CCTA- and the CA-equipment had been upgraded).For the Period 2009 total ERD of the non-invasive approach was significantly larger compared to the invasive approach (28.45 ± 5.37 mSv versus 15.79 ± 7.95 mSv, respectively; P 0.0001). For Period 2011, despite the significant decrease in ERD for both groups (P0.0001 for both), the ERD remained higher for the non-invasive approach compared to the invasive approach (16.67 ± 10.45 mSv vs. 10.36 ± 5.87 mSv, respectively; P 0.0001). Simulation of various diagnostic scenarios showed cumulative radiation dose is the lowest when a first positive test is followed by an invasive strategy.To obtain anatomic and physiologic information in patients with suspected CAD, the combination of CA and FFR is associated with lower ERD than the combination of CCTA and SPECT.

Objectives The aim of this study was to compare the angiographic changes in coronary geometry of the bioresorbable vascular scaffolds (BVS) and metallic platform stent (MPS) between baseline and follow-up. Background Coronary geometry changes after stenting might result in wall shear stress changes and adverse events. The BVS have better conformability, compared with MPS, but still modify artery geometry. It is uncertain whether the BVS resorption can restore the coronary anatomical configuration at midterm follow-up. Methods All patients of the ABSORB (A Clinical Evaluation of the Bioabsorbable Everolimus Eluting Coronary Stent System [BVS EECSS] in the Treatment of Patients With de Novo Native Coronary Artery Lesions) and SPIRIT (A Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Patients With de Novo Native Coronary Artery Lesions) trials treated with a single 3.0 x 18 mm device and imaged at baseline and 6- to 12-month follow-up were eligible. Coronary geometry changes were assessed with quantitative angiography as changes in curvature and angulation. Curvature and angulation changes between systole and diastole were investigated to assess hinging movements of the coronary artery. Results One hundred sixty-one patients (86 BVS, and 75 MPS) were included. Baseline angiographic characteristics were similar. From post-implantation to follow-up, curvature increased 8.4% (p < 0.01) with BVS and decreased 1.9% (p = 0.54) with MPS; p = 0.01. Angulation increased 11.3% with BVS (p < 0.01) and 3.8% with MPS (p = 0.01); p < 0.01. From pre-implantation to follow-up, BVS decreased 3.4% the artery curvature (p = 0.05) and 3.9% the artery angulation (p = 0.16), whereas MPS presented with 26.1% decrease in curvature (p < 0.01) and 26.9% decrease in angulation (p < 0.01), being larger with MPS (p < 0.01, both). Hinging movements in curvature from pre-implantation to follow-up decreased 19.7% with BVS and 39.0% with MPS (p = 0.27) and decreased 3.9% with BVS and 26.9% with MPS in angulation (p < 0.01). Conclusions At midterm follow-up, the BVS tended to restore the coronary configuration and the systodiastolic movements to those seen before implantation. The coronary geometry remained similar to that seen at after implantation with MPS. (A Clinical Evaluation of the Bioabsorbable Everolimus Eluting Coronary Stent System [BVS EECSS] in the Treatment of Patients With de Novo Native Coronary Artery Lesions; NCT00856856) (J Am Coll Cardiol Intv 2011;4:789-99) (C) 2011 by the American College of Cardiology Foundation

AIMS To assess the safety and efficacy of the XTENT customisable drug-eluting stent system in the treatment of patients with single long or multiple coronary lesions referred for PCI. METHODS AND RESULTS The CUSTOM-II trial enrolled 100 patients with de novo lesions in native coronary arteries presenting with either single long lesions (n=69) of > or =20 mm length or up to two lesions with a total cumulative anticipated stent length of 60 mm of stent (n=31). Patients were assessed angiographically at six months, and clinically at one year. Of the 100 patients enrolled, nine patients experienced a MACE, including five patients whose MACE occurred during index hospitalisation (two non-Q-MI, two Q-MI and one probable stent thrombosis-related death), and four target lesion revascularisations (TLR) at six months. No MACE or stent thrombosis was reported between six and 12 months follow-up. In-segment late loss at 6-months was 0.22 +/- 0.28 mm, and in-stent late loss had a range of 0.31 +/- 0.31 mm. CONCLUSIONS The XTENT customisable stent is clinically safe and efficacious as judged by angiographic and clinical variables through 12 months follow-up. Further follow-up and larger randomised comparative studies are needed for its clinical positioning.

Patients with suspected coronary artery disease often undergo coronary angiography without prior non-invasive functional stress testing, mainly because of logistic reasons, shortcomings of the non-invasive tests, and a more widespread confidence in invasive techniques. The availability in the catheterization laboratory of the pressure-derived fractional flow reserve (FFR) has provided the interventional cardiologist with the ideal tool for appropriate decision-making based on the functional significance of the coronary stenosis detected at the angiogram. In fact, FFR allows a more refined and individualized understanding of the true severity of coronary artery disease, and, therefore, a more appropriate selection of the epicardial lesions to be treated, especially in patients with dubious lesions and complex disease. A clinical decision-making based on coronary pressure measurement results in a more effective strategy than placing stents on a "trial and error" basis. This is particularly true in case of drug-eluting stents where an approach based on an indiscriminate multi-stenting will annihilate the benefits of these new stents and be unacceptably expensive. In addition, many angiographically mild stenoses happen to be hemodynamically significant and, therefore, deserve revascularization, especially in the drug-eluting stent era.

The coronary flow velocity acceleration at the stenotic site (SVA), defined as a > or = 50% increase in resting stenotic velocity when compared with the reference segment, has been shown to be highly sensitive and specific for the diagnosis of a hemodynamically significant stenosis. In this study, we describe the value of postprocedural SVA for the prediction of a lack of improvement in functional activity at long-term follow-up balloon angioplasty (BA). We investigated the improvement in functional activity in patients undergoing single native vessel angioplasty and intracoronary Doppler (before BA, after BA, and again at 6-month follow-up) as part of the Doppler Endpoints Balloon Angioplasty Trial Europe (DEBATE) I trial. Lack of improvement was defined as no change in Duke Activity Status Index (DASI) at 6-month follow-up, whereas SVA was defined as > or = 50% elevation in resting velocity at the treated area compared with the distal measurement. SVA was found more frequently in patients without improvement in DASI (45% vs 31%, P =.03). Similar percent diameter stenosis and coronary flow velocity reserve were observed in patients with and those without improvement in DASI at follow-up. By multivariate regression analysis, the presence of SVA (P = .029; odds ratio, 1.97; 95% confidence interval, 1.07 to 3.63) and an elevated DASI at baseline (P < .001; odds ratio, 1.05; 95% confidence interval, 1.03 to 1.07) were associated with a lack of improvement at follow-up. The detection of SVA was associated with failure of improvement in functional activity at follow-up after coronary intervention

Aims Evaluation of angiographical and intracoronary Doppler-derived parameters of coronary stenosis severity. Methods and Results A total of 225 patients with one-vessel disease were studied before PTCA and at 6 months follow-up. Exercise electrocardiography was performed to document presence (n=157) or absence (n=138) of an ST segment shift (greater than or equal to 0.1 mV). Intracoronary blood flow velocity analysis was performed to determine the proximal/distal flow velocity ratio, the distal diastolic/systolic flow velocity ratio and coronary flow velocity reserve. Receiver operator characteristic curves were calculated to assess the predictive value of these variables compared with the exercise test. The distal coronary flow velocity reserve demonstrated the best linear correlation for both percentage diameter stenosis and minimum lumen diameter (r=0.67 and r=0.66; P Conclusions The distal coronary flow velocity reserve is the best intracoronary Doppler parameter for evaluation of coronary narrowings. Angiographical estimates of coronary lesion severity and distal coronary flow velocity reserve are good and independent predictors for the assessment of functional severity of coronary stenosis, emphasizing the complementary role of these parameters for clinical decision making. (C) 2000 The European Society of Cardiology.

Myocardial perfusion reserve (hyperemic divided by basal myocardial blood flow) describes vasodilator responsiveness of coronaryresistive vessels. The effect of aging and gender on myocardial perfusion reserve remains controversial. Methods: We studied 56 normal volunteers (21 women, 35 men; aged 50 +/- 20 yr, range 21-86 yr) with O-15-water PET to measure myocardial blood flow during basal and hyperemic stales with intravenous dipyridamole (0.56 mg/kg, n = 46) or adenosine (140 mu g/kg/min, n = 10). For comparative analysis, patients were grouped according to age

Coronary artery disease (CAD) continues to be the leading cause of mortality and morbidity in developed countries. Assessment of pre-test probability (PTP) based on patient's characteristics, gender and symptoms, help to identify more accurate patient's clinical likelihood of coronary artery disease. Consequently, non-invasive imaging tests are performed more appropriately to rule in or rule out CAD rather than invasive coronary angiography (ICA). Coronary computed tomography angiography (CCTA) is the first-line non-invasive imaging technique in patients with suspected CAD and could be used to plan and guide coronary intervention. Invasive coronary angiography remains the gold-standard method for the identification and characterization of coronary artery stenosis. However, it is recommended in patients where the imaging tests are non-conclusive, and the clinical likelihood is very high, remembering that in clinical practice, approximately 30 to 70% of patients with symptoms and/or signs of ischemia, referred to coronary angiography, have non obstructive coronary artery disease (INOCA). In this contest, physiology and imaging-guided revascularization represent the cornerstone of contemporary management of chronic coronary syndromes (CCS) patients allowing us to focus specifically on ischemia-inducing stenoses. Finally, we also discuss contemporary medical therapeutic approach for secondary prevention. The aim of this review is to provide an updated diagnostic and therapeutic approach for the management of patients with stable coronary artery disease.

Background Coronary microvascular dysfunction is a powerful prognostic factor in patients with coronary artery disease. We investigated the role of reactive digital hyperemia peripheral arterial tonometry (RH-PAT) as a non-invasive tool to identify patients with impaired coronary microvasculature. Methods Patients undergoing elective coronary angiography were consecutively assessed for peripheral microvascular endothelial function before coronary angiography: both the Reactive Hyperemic Index (RHI) and the Framingham reactive hyperemic index (Endoscore) were measured. During coronary angiography, the Index of microvascular resistance (IMR) was measured in all patients, and an IMR value > 25 identified patients with coronary microvascular impairment. Results A total of 47 patients with chronic coronary syndromes candidate to coronary angiography were included. Those with coronary microvascular impairment (n = 18 [38%]) presented with significantly lower RHI (1.68 ± 0.38 vs. 1.94 ± 0.93, p = 0.04) and Endoscore 0.50 ± 0.23 vs. 0.64 ± 0.23, p = 0.04) values as compared with patients with preserved coronary microvasculature. A significant relationship was observed between IMR with both RHI (r = 0.35, p = 0.02) and Endoscore (r = 0.34, p = 0.02). At the multivariable analysis, RHI and Endoscore were the only independent predictors of an IMR > 25. Conclusions Our study demonstrates that digital reactive hyperemia indexes are lower in patients with high IMR values, suggesting a role for RH-PAT as non-invasive tool for identifying patients with coronary microvascular impairment.

Background: Graft occlusion after coronary artery bypass graft surgery (CABG) has been associated with native coronary artery competitive flow. Objectives: The present study aims to characterize the functional progression of coronary artery disease (CAD) in native vessels after CABG, and to assess the relationship between preoperative FFR as derived from angiography and graft occlusion. Methods: Multicenter study of consecutive patients undergoing CABG between 2013 and 2018, in whom a follow-up angiogram had been performed. Serial vessel-fractional flow reserve (vFFR) analyses were obtained in each major native coronary vessel before and after CABG, excluding post-anastomotic segments and graft conduits. Results: In 73 patients, serial angiograms were suitable for vFFR analysis, including 118 grafted (86 arterial and 32 saphenous grafts) and 64 non-grafted vessels. The median time between CABG and follow-up angiography was 2.4 years [IQR 1.5, 3.3]. Functional CAD progression, by means of decline in vFFR, was observed in grafted but not in non-grafted vessels (delta vFFR in grafted vessels 0.10 [IQR 0.05, 0.18] vs. 0.01 [IQR -0.01, 0.03], in non-grafted vessels, p < 0.001). Preoperative vFFR predicted graft occlusion (AUC: 0.66, 95% CI 0.52 to 0.80, p = 0.031). Conclusions: In patients undergoing CABG, preoperative vFFR derived from conventional angiograms without use of pressure wire was able to predict graft occlusion. Graft occlusion was more frequent in vessels with high vFFR values. Grafted native coronary vessels exhibited accelerated functional CAD progression, whereas in non-grafted native coronaries the functional status remained unchanged.

Importance Whether the improvement in myocardial perfusion provided by percutaneous coronary intervention (PCI) is associated with symptomatic relief or improved outcomes has not been well investigated. Objective To investigate the prognostic value of the improvement in fractional flow reserve (FFR) after PCI (ΔFFR) on patients’ symptoms and 2-year outcomes. Design, Setting, and Participants This study is a post hoc analysis of data from patients undergoing FFR-guided PCI in the randomized clinical trials Fractional Flow Reserve vs Angiography for Multivessel Evaluation (FAME) 1 (NCT00267774; 2009) and FAME 2 (NCT01132495; 2012), with inclusion of 2 years of follow-up data. The FAME 1 trial included patients with multivessel coronary artery disease from 20 medical centers in Europe and the United States. The FAME 2 trial included patients with stable coronary artery disease involving up to 3 vessels from 28 sites in Europe and North America. Lesions from the group in the FAME 1 trial from whom FFR was measured and the group in the FAME 2 trial who received FFR-guided PCI plus medical therapy were analyzed. Data analysis occurred from May 2017 to May 2018. Interventions Measure of post-PCI FFR. Main Outcomes and Measures Vessel-oriented clinical events at 2 years, a composite of cardiac death, target vessel-associated myocardial infarction, and target vessel revascularization. Results This analysis included 639 patients from whom pre-PCI and post-PCI FFR values were available. Of their 837 lesions, 277 were classified into the lowest tertile (ΔFFR≤0.18), 282 into the middle tertile (0.19≤ΔFFR≤0.31), and 278 into the highest tertile (ΔFFR>0.31). Vessel-oriented clinical events were significantly more frequent in the lowest tertile (n = 25 of 277 [9.1%]) compared with the highest tertile (n = 13 of 278 [4.7%]; hazard ratio, 2.01 [95% CI, 1.03-3.92]; P = .04). In addition, a significant association was observed between ΔFFR and symptomatic relief (odds ratio, 1.33 [95% CI, 1.02-1.74]; P = .02). Conclusions and Relevance In this analysis of 2 randomized clinical trials, the larger the improvement in FFR, the larger the symptomatic relief and the lower the event rate. This suggests that measuring FFR before and after PCI provides clinically useful information.

Background Global fractional flow reserve (FFR) (ie, the sum of the FFR values in the 3 major coronary arteries) is a physiologic correlate of global atherosclerotic burden. The objective of the present study was to investigate the value of global FFR in predicting long‐term clinical outcome of patients with stable coronary artery disease but no ischemia‐inducing stenosis. Methods and Results We studied major adverse cardiovascular events (MACEs: all‐cause death, myocardial infarction, and any revascularization) after 5 years in 1122 patients without significant stenosis (all FFR >0.80; n=275) or with at least 1 significant stenosis successfully treated by percutaneous coronary intervention (ie, post–percutaneous coronary intervention FFR >0.80; n=847). The patients were stratified into low, mid, or high tertiles of global FFR (≤2.80, 2.80–2.88, and ≥2.88). Patients in the lowest tertile of global FFR showed the highest 5‐year MACE rate compared with those in the mid or high tertile of global FFR (27.5% versus 22.0% and 20.9%, respectively; log‐rank P =0.040). The higher 5‐year MACE rate was mainly driven by a higher rate of revascularization in the low global FFR group (16.4% versus 11.3% and 11.8%, respectively; log‐rank P =0.038). In a multivariable model, an increase in global FFR of 0.1 unit was associated with a significant reduction in the rates of MACE (hazard ratio [HR], 0.988; 95% CI, 0.977–0.998; P =0.023), myocardial infarction (HR, 0.982; 95% CI, 0.966–0.998; P =0.032), and revascularization (HR, 0.985; 95% CI, 0.972–0.999; P =0.040). Conclusions Even in the absence of ischemia‐producing stenoses, patients with a low global FFR, physiologic correlate of global atherosclerotic burden, present a higher risk of MACE at 5‐year follow‐up.

Background: During fractional flow reserve (FFR) measurement, the simple presence of the guiding catheter (GC) within the coronary ostium might create artificial ostial stenosis, affecting the hyperemic flow. We aimed to investigate whether selective GC engagement of the coronary ostium might impede hyperemic flow, and therefore impact FFR measurements and related clinical decision-making. Methods: In the DISENGAGE (Determination of Fractional Flow Reserve in Intermediate Coronary Stenosis With Guiding Catheter Disengagement) registry, FFR was prospectively measured twice (with GC engaged [FFR eng ] and disengaged [FFR dis ]) in 202 intermediate stenoses of 173 patients. We assessed (1) whether ΔFFR eng –FFR dis was significantly different from the intrinsic variability of repeated FFR measurements (test-retest repeatability); (2) whether the extent of ΔFFR eng –FFR dis could be clinically significant and therefore able to impact clinical decision-making; and (3) whether ΔFFR eng –FFR dis related to the stenosis location, that is, proximal and middle versus distal coronary segments. Results: Overall, FFR significantly changed after GC disengagement: FFR eng 0.84±0.08 versus FFR dis 0.80±0.09, P eng –FFR dis , proximal and middle 0.04±0.03 versus distal segments 0.03±0.03; P =0.042). Conclusions: GC disengagement results in a shift of FFR values from above to below the clinical cutoff FFR value of 0.80 in 1 out of 5 measurements. This occurs mostly when the stenosis is located in proximal and middle coronary segments and the FFR value is close to the cutoff value.

Objectives The present study aimed at determining the accuracy and reproducibility of motorized FFR pullbacks in patients with stable coronary artery disease. Background Fractional flow reserve (FFR) is recommended for decision making regarding myocardial revascularization. The distribution of epicardial resistance along coronary vessels can be assessed using FFR pullbacks. Methods Duplicated FFR pullbacks were acquired using a motorized device at a speed of 1 mm/s in intermediate coronary stenosis. In addition, a single FFR value was measured at an anatomical landmark. The agreement between FFR measurements was assessed using the Bland-Altman method, Pearson's correlation coefficient and area under the pullback curve (AUPC). Results In 20 vessels, 37,326 FFR values were obtained. The mean FFR from the pullbacks was 0.91 ± 0.08 whereas the mean FFR at the distal location was 0.85 ± 0.09. The mean difference between pullbacks was -0.002 (LOA -0.058 to 0.054). The difference in AUPC between the two FFR pullbacks was 2.1 ± 1.6%. At pre-specified anatomical locations, the mean difference between the FFR derived from the pullback data and the measured FFR was 0 (LOA -0.040 to 0.039). The repeatability of the distal FFR measurement was high (bias -0.003, LOA -0.046 to 0.041). Conclusion A motorized FFR pullback was accurate to assess the distribution of epicardial resistance in patients with intermediate coronary artery disease. The reproducibility of the FFR pullback was high. Further studies are required to determine the potential usefulness of a hyperemic FFR pullback strategy for decision making and treatment planning.

Aims: Fractional flow reserve (FFR) pullback allows to assess the distribution of pressure loss along the coronary vessels. FFR derived from CT (FFR CT) provides a virtual pullback curve that may also aid in the assessment of the distribution of epicardial coronary resistance in the non-invasive setting. The present study aims to determine the accuracy of the virtual FFR CT pullback curve using a motorized invasive FFR pullback as reference in patients with stable coronary artery disease. Methods and results: FFR values were extracted from coronary vessels at approximately 1 mm to generate pullback curves. Invasive motorized FFR pullbacks were acquired using a dedicated device at a speed of 1 mm/s. A total of 3172 matched FFR CT and FFR values were obtained in 24 vessels. The correlation coefficient between FFR CT and FFR was 0.76 (95%CI 0.75 to 0.78; p < 0.001). The area under the pullback curve was similar between FFR CT and invasive FFR (79.0 ± 16.1 vs. 85.3 ± 16.4, p = 0.097). The mean difference in lesion gradient between FFR CT and FFR was −0.07 (LOA -0.26 to 0.13) whereas in non-obstructive segments was −0.01 (LOA -0.06 to 0.05). Conclusion: The evaluation of epicardial coronary resistance using coronary CT angiography with FFR CT was feasible. FFR CT virtual pullback appears to be accurate for the evaluation of pressure gradients. FFR CT has the potential to identify the pathophysiological pattern of coronary artery disease in the non-invasive setting.

Coronary computed tomography angiography (CCTA) is at the frontline of the diagnostic strategies to detect coronary artery disease (CAD). Anatomical information have proven to be insufficient to detect hemodynamic significant epicardial stenosis. In the present invited review we discuss on FFRCT and stress CTP, emerging technologies for an accurate and comprehensive evaluation of patients with suspected CAD, offering both anatomical (i.e. luminal and plaque) and functional assessment in one single technique.

Objectives: The aim of this study was to compare clinical outcomes of different bifurcation percutaneous coronary intervention (PCI) techniques. Background: Despite several randomized trials, the optimal PCI technique for bifurcation lesions remains a matter of debate. Provisional stenting has been recommended as the default technique for most bifurcation lesions. Emerging data support double-kissing crush (DK-crush) as a 2-stent technique. Methods: PubMed and Scopus were searched for randomized controlled trials comparing PCI bifurcation techniques for coronary bifurcation lesions. Outcomes of interest were major adverse cardiovascular events (MACE). Secondary outcomes of interest were cardiac death, myocardial infarction, target vessel or lesion revascularization, and stent thrombosis. Summary odds ratios (ORs) were estimated using Bayesian network meta-analysis. Results: Twenty-one randomized controlled trials including 5,711 patients treated using 5 bifurcation PCI techniques were included. Investigated techniques were provisional stenting, T stenting/T and protrusion, crush, culotte, and DK-crush. Median follow-up duration was 12 months (interquartile range: 9 to 36 months). When all techniques were considered, patients treated using the DK-crush technique had less occurrence of MACE (OR: 0.39; 95% credible interval: 0.26 to 0.55) compared with those treated using provisional stenting, driven by a reduction in target lesion revascularization (OR: 0.36; 95% credible interval: 0.22 to 0.57). No differences were found in cardiac death, myocardial infarction, or stent thrombosis among analyzed PCI techniques. No differences in MACE were observed among provisional stenting, culotte, T stenting/T and protrusion, and crush. In non–left main bifurcations, DK-crush reduced MACE (OR: 0.42; 95% credible interval: 0.24 to 0.66). Conclusions: In this network meta-analysis, DK-crush was associated with fewer MACE, driven by lower rates of repeat revascularization, whereas no significant differences among techniques were observed for cardiac death, myocardial infarction, and stent thrombosis. A clinical benefit of 2-stent techniques was observed over provisional stenting in bifurcation with side branch lesion length ≥10 mm.

Aims Significant platelet activation after long stented coronary segments has been associated with periprocedural microvascular impairment and myonecrosis. In long lesions treated either with an everolimus-eluting bioresorbable vascular scaffold (BVS) or an everolimus-eluting stent (EES), we aimed to investigate (a) procedure-related microvascular impairment, and (b) the relationship of platelet activation with microvascular function and related myonecrosis. Methods and results Patients (n=66) undergoing elective percutaneous coronary intervention (PCI) in long lesions were randomised 1:1 to either BVS or EES. The primary endpoint was the difference between groups in changes of pressure-derived corrected index of microvascular resistance (cIMR) after PCI. Periprocedural myonecrosis was assessed by high-sensitivity cardiac troponin T (hs-cTnT), platelet reactivity by high-sensitivity adenosine diphosphate (hs-ADP)-induced platelet reactivity with the Multiplate Analyzer. Post-dilatation was more frequent in the BVS group, with consequent longer procedure time. A significant difference was observed between the two groups in the primary endpoint of ΔcIMR (p=0.04). hs-ADP was not different between the groups at different time points. hs-cTnT significantly increased after PCI, without difference between the groups. Conclusions In long lesions, BVS implantation is associated with significant acute reduction in IMR as compared with EES, with no significant interaction with platelet reactivity or periprocedural myonecrosis.

Background: In diabetic patients with multivessel coronary artery disease, coronary artery bypass grafting (CABG) has shown long-term benefits over percutaneous coronary intervention (PCI). Physiology-guided PCI has shown to improve clinical outcomes in multivessel coronary artery disease, though its impact in diabetic patients has never been investigated. We evaluated long-term clinical outcomes of diabetic patients with multivessel coronary artery disease treated with fractional flow reserve (FFR)–guided PCI compared with CABG. Methods: From 2010 to 2018, 4622 diabetic patients undergoing coronary angiography were screened for inclusion. The inclusion criterion was the presence of at least 2-vessel disease defined as with diameter stenosis ≥50%, in which at least 1 intermediate stenosis (diameter stenosis, 30%–70%) was treated or deferred according to FFR. Inverse probability of treatment weighting analysis was used to account for baseline differences with a contemporary cohort of patients treated with CABG. The primary end point was major adverse cardiovascular and cerebrovascular events, defined as all-cause death, myocardial infarction, revascularization, or stroke. Results: A total of 418 patients were included in the analysis. Among them, 209 patients underwent CABG and 209 FFR-guided PCI. At 5 years, the incidence of major adverse cardiovascular and cerebrovascular events was higher in the FFR-guided PCI versus the CABG group (44.5% versus 31.9%; hazard ratio, 1.60 [95% CI, 1.15–2.22]; P =0.005). No difference was found in the composite of all-cause death, myocardial infarction, or stroke (28.8% versus 27.5%; hazard ratio, 1.05 [95% CI, 0.72–1.53]; P =0.81). Repeat revascularization was more frequent with FFR-guided PCI (24.9% versus 8.2%; hazard ratio, 3.51 [95% CI, 1.93–6.40]; P Conclusions: In diabetic patients with multivessel coronary artery disease, CABG was associated with a lower rate of major adverse cardiovascular and cerebrovascular events compared with FFR-guided PCI, driven by a higher rate of repeat revascularization. At 5-year follow-up, no difference was observed in the composite of all-cause death, myocardial infarction, or stroke between CABG and FFR-guided PCI. Graphic Abstract: A graphic abstract is available for this article.

BACKGROUND: Coronary microvascular dysfunction before percutaneous coronary intervention (PCI) predicts PCI-related myocardial injury in patients with stable coronary artery disease (CAD). Whether the dynamic changes of the microcirculation during PCI might be associated with the occurrence of procedure-related myocardial injury and infarction is still unclear. We aimed to investigate the impact of pre- and post-PCI microvascular function, evaluated with the index of microvascular resistance (IMR) on the occurrence of PCI-related myocardial injury and infarction. METHODS: In consecutive patients with stable CAD referred for elective PCI, coronary physiological indexes, including IMR, were measured before and after revascularization. High sensitivity Troponin T (hs-TnT) was assessed up to 24 h after PCI, and PCI-related myocardial injury and type 4a myocardial infarction (MI) were defined according to the fourth universal definition of myocardial infarction. RESULTS: In the 50 patients enrolled, a significant correlation was found between maximum post-PCI hs-Tn and IMR, both at baseline (rho = 0.309, p=0.029) and post-PCI (rho = 0.378, p=0.007). Patients who developed type 4a MI, compared with patients who did not, presented significantly higher IMR levels, both at baseline (28.3 ± 12.2 vs. 19.6 ± 8.8, p=0.020) and post-PCI (45.4 ± 21.3 vs. 21.6 ± 11.2, p 38 showed significantly higher maximum post-PCI hs-Tn levels (105.4 [49.4-126.9] vs. 22.4 [11.7-38.6] ng/ml, p

BACKGROUND Diffuse atherosclerosis is commonly observed in angiographically normal segments in patients with stable coronary artery disease (CAD). The distribution of epicardial resistance along the vessel can be evaluated using coronary physiology. OBJECTIVES The purpose of this study was to characterize the pathophysiological patterns of CAD using invasive pressure pullbacks during continuous hyperemia. METHODS In this prospective, multicenter study of patients undergoing clinically-indicated coronary angiography due to stable angina, a pressure-wire pullback device was set at a speed of 1 mm/s. Based on coronary angiography and on the fractional flow reserve (FFR) pullback curve, the patterns of CAD were adjudicated as focal, diffuse, or a combination of both. The distribution of epicardial resistance was characterized using the hyperemic pullback pressure gradients (PPGs). The PPG index, a continuous metric based on the magnitude of pressure drop over 20 mm and on the extent of functional disease was computed to determine the pattern of CAD. Low PPG index indicates diffuse CAD. RESULTS A total of 158 vessels (n = 117) were included. Overall, 984,813 FFR values were used to generate 100 FFR pullback curves. Using coronary physiology, 36% of the vessel disease patterns were reclassified compared to angiography. The median of maximal PPG over 20 mm was 0.083 (interquartile range: 0.063 to 0.118) FFR units, and the mean extent of functional disease was 39.3 +/- 21.3 mm. The mean PPG index was 0.58 +/- 0.18 and differentiated pathophysiological focal and diffuse disease (p < 0.001). CONCLUSIONS Pathophysiological patterns of CAD can be characterized by motorized hyperemic PPGs. The evaluation of the FFR pullback curve reclassified one-third of the vessels' disease patterns compared with conventional angiography. The PPG index is a novel metric that quantifies the distribution of epicardial resistance and discriminates focal from diffuse CAD., BACKGROUND Diffuse atherosclerosis is commonly observed in angiographically normal segments in patients with stable coronary artery disease (CAD). The distribution of epicardial resistance along the vessel can be evaluated using coronary physiology. OBJECTIVES The purpose of this study was to characterize the pathophysiological patterns of CAD using invasive pressure pullbacks during continuous hyperemia. METHODS In this prospective, multicenter study of patients undergoing clinically-indicated coronary angiography due to stable angina, a pressure-wire pullback device was set at a speed of 1 mm/s. Based on coronary angiography and on the fractional flow reserve (FFR) pullback curve, the patterns of CAD were adjudicated as focal, diffuse, or a combination of both. The distribution of epicardial resistance was characterized using the hyperemic pullback pressure gradients (PPGs). The PPG index, a continuous metric based on the magnitude of pressure drop over 20 mm and on the extent of functional disease was computed to determine the pattern of CAD. Low PPG index indicates diffuse CAD. RESULTS A total of 158 vessels (n = 117) were included. Overall, 984,813 FFR values were used to generate 100 FFR pullback curves. Using coronary physiology, 36% of the vessel disease patterns were reclassified compared to angiography. The median of maximal PPG over 20 mm was 0.083 (interquartile range: 0.063 to 0.118) FFR units, and the mean extent of functional disease was 39.3 +/- 21.3 mm. The mean PPG index was 0.58 +/- 0.18 and differentiated pathophysiological focal and diffuse disease (p < 0.001). CONCLUSIONS Pathophysiological patterns of CAD can be characterized by motorized hyperemic PPGs. The evaluation of the FFR pullback curve reclassified one-third of the vessels' disease patterns compared with conventional angiography. The PPG index is a novel metric that quantifies the distribution of epicardial resistance and discriminates focal from diffuse CAD. (C) 2019 by the American College of Cardiology Foundation.

The reliability of fractional flow reserve (FFR) in aortic stenosis (AS) has been questioned because of the uncertain response to vasodilators. A retrospective multicenter cohort of 114 AS patients who underwent coronary physiology assessment was compared with 154 controls before and after propensity matching adjustment. The difference between resting distal coronary vs aortic pressure ratio (Pd/Pa) and FFR (ΔPd/Pa-FFR) was tested against the severity of AS. ΔPd/Pa-FFR was not influenced by the severity of AS in terms of aortic valve area (r = - 0.02, p = 0.83) and gradient (r = - 0.05, p = 0.64) or by the left ventricle hypertrophy (r = - 0.03, p = 0.88). Conversely, ΔPd/Pa-FFR was influenced by the presence of diabetes (r = - 0.24, p = 0.005), peripheral vascular disease (r = - 0.16, p = 0.047), and chronic kidney disease (r = - 0.19, p = 0.03). No significant difference was observed in the ΔPd/Pa-FFR between patients with AS and matched controls. Further studies are warranted to validate the FFR-guided revascularization in patients with AS.

The presence at coronary angiography of a stenosis in the proximal left anterior descending coronary artery (LAD) bears a poor prognosis [(1)][1]. Given the known limitations of angiography to define severity of stenosis, fractional flow reserve (FFR) is now considered the standard of reference to

SummaryBackgroundDrug-eluting stents (DES) are more effective than bare-metal stents (BMS) in small coronary vessel disease. Whether this is true in elderly patients, it is unclear, as frailty and a high rate of comorbidities could increase the rate of DES-related complications.AimsTo assess procedural and long-term clinical outcomes of elderly patients with small vessel disease treated with DES or BMS.MethodsConsecutive elderly patients (≥ 75 years old) treated with stenting of native small coronary arteries (reference vessel diameter and implanted stent

ObjectivesThis study investigated the influence of intracoronary enalaprilat on coronary microvascular function and peri-procedural outcome measures in patients with stable angina undergoing percutaneous coronary intervention (PCI).BackgroundIntracoronary angiotensin-converting enzyme inhibitors have been shown to relieve myocardial ischemia in stable patients and to improve epicardial flow in patients with ST-segment elevation myocardial infarction. Yet, it is still unclear whether these effects are mediated by a modulation of the coronary microcirculation.MethodsWe randomly assigned 40 patients to receive either an intracoronary bolus of enalaprilat (50 μg) or placebo before elective PCI. The index of microvascular resistance was measured at baseline, 10 minutes after study drug administration, and after PCI. High-sensitivity cardiac troponin T was measured as a marker of myocardial injury.ResultsInfusion of enalaprilat resulted in a significant reduction in index of microvascular resistance (27 ± 11 at baseline vs. 19 ± 9 after drug vs. 15 ± 8 after PCI), whereas a significant post-procedural increase in index of microvascular resistance levels was observed in the placebo group (24 ± 15 at baseline vs. 24 ± 15 after drug vs. 33 ± 19 after PCI). Index of microvascular resistance levels after PCI were significantly lower in the enalaprilat group (p < 0.001). Patients pre-treated with enalaprilat also showed lower peak values (mean: 21.7 ng/ml, range: 8.2 to 34.8 ng/ml vs. mean: 32.3 ng/ml, range: 12.6 to 65.2 ng/ml, p = 0.048) and peri-procedural increases of high-sensitivity cardiac troponin T (mean: 9.9 ng/ml, range: 2.7 to 19.0 ng/ml vs. mean: 26.6 ng/ml, range: 6.3 to 60.5 ng/ml, p = 0.025).ConclusionsIntracoronary enalaprilat improves coronary microvascular function and protects myocardium from procedure-related injury in patients with coronary artery disease undergoing PCI. Larger studies are warranted to investigate whether these effects of enalaprilat could result into a significant clinical benefit.

Summary. Background: Percutaneous coronary intervention (PCI) modulates platelet reactivity (PR). Objectives: To assess: (i) the impact of coronary interventions on periprocedural variations (Δ) of PR; (ii) whether ΔPR correlates with periprocedural myocardial infarction (PMI); and (iii) the mechanisms of these variations in vitro. Methods and results: We enrolled 65 patients on aspirin (80–100 mg day−1) and clopidogrel (600 mg, 12 h before PCI): 15 with coronary angiography (CA group), 40 with PCI (PCI group), and 10 with rotational atherectomy plus PCI (RA group). PR was assessed by ADP, high-sensitivity ADP and thrombin receptor activator peptide 6 tests prior to, immediately after and 24 h after the procedure. E-selectin and ICAM-1 were assessed prior to and immediately after the procedure. In vitro, PR was measured during pulsatile blood flow at baseline, after balloon inflation and after stent implantation in six porcine carotid arteries and five plastic tubes. PR declined in the CA group, but significantly increased in the PCI and RA groups immediately postprocedure, and decreased to baseline at 24 h. ΔPR increased across the three groups (P

International audience; BACKGROUND: In patients with coronary artery disease, clinical outcome depends on the extent of reversible myocardial ischemia. Whether the outcome also depends on the severity of the stenosis as determined by fractional flow reserve (FFR) remains unknown. OBJECTIVES: This study sought to investigate the relationship between FFR values and vessel-related clinical outcome. METHODS: We prospectively studied major adverse cardiovascular events (MACE) at 2 years in 607 patients in whom all stenoses were assessed by FFR and who were treated with medical therapy alone. The relationship between FFR and 2-year MACE was assessed as a continuous function. Logistic and Cox proportional hazards regression models were used to calculate the average decrease in the risk of MACE per 0.05-U increase in FFR. RESULTS: MACE occurred in 272 (26.5%) of 1,029 lesions. Target lesions with diameter stenosis \textgreater/=70% were more often present in the MACE group (p \textless 0.01). Median FFR was significantly lower in the MACE group versus the non-MACE group (0.68 [interquartile range: 0.54 to 0.77] vs. 0.80 [interquartile range: 0.70 to 0.88]; p \textless 0.01). The cumulative incidence of MACE significantly increased with increasing FFR quartiles. An average decrease in MACE per 0.05-unit increase in FFR was statistically significant even after adjustment for all clinical and angiographic features (odds ratio: 0.81; 95% confidence interval: 0.76 to 0.86]). The strongest increase in MACE occurred for FFR values between 0.80 and 0.60. In multivariable Cox regression analysis, FFR was significantly associated with MACE up to 2 years (hazard ratio: 0.87; 95% confidence interval: 0.83 to 0.91]). CONCLUSIONS: In patients with stable coronary disease, stenosis severity as assessed by FFR is a major and independent predictor of lesion-related outcome. (FAME II - Fractional Flow Reserve [FFR] Guided Percutaneous Coronary Intervention [PCI] Plus Optimal Medical Treatment [OMT] Verses OMT; NCT01132495).

Objectives This study sought to evaluate the long-term clinical outcome of patients with an angio-graphically intermediate left anterior descending coronary artery (LAD) stenosis in whom the revascularization strategy was based on fractional flow reserve (FFR). Background When revascularization is based mainly on angiographic guidance, a number of hemodynamically nonsignificant stenoses will be revascularized. Methods In 730 patients with a 30% to 70% isolated stenosis in the proximal LAD and no significant valvular disease, FFR measurements were obtained to guide treatment strategy. When FFR was >= 0.80, the patients (n = 564) were treated medically (medical group); when FFR was < 0.80, the patients (n = 166) underwent a revascularization procedure (revascularization group; 13% coronary artery bypass graft surgery and 87% percutaneous coronary intervention). A 100% long-term clinical follow-up (median follow-up: 40 months) was obtained. The 5-year survival of the medical group was compared with that of a reference population. For each patient, 4 controls were selected from an age- and sex-matched control population. Results The 5-year survival estimate was 92.9% in the medical group versus 89.6% in the controls (p = 0.74). The mean diameter stenosis was significantly smaller in the medical than in the revascularization group (39 +/- 14% vs. 54 +/- 13%, p < 0.0001), but there was a large overlap between both groups. The 5-year event-free survival estimates (death, myocardial infarction, and target vessel revascularization) were 89.7% and 68.5%, respectively (p < 0.0001). Conclusions Medical treatment of patients with a hemodynamically nonsignificant stenosis (FFR >= 0.80) in the proximal LAD is associated with an excellent long-term clinical outcome with survival at 5 years similar to an age- and sex-matched control population. (J Am Coll Cardiol Intv 2011;4: 1175-82) (C) 2011 by the American College of Cardiology Foundation

An interesting case of acute coronary syndrome occurring shortly after a cardiac catheterization is reported. Different tests and imaging modalities for coronary artery disease have been performed in this patient. The potential for integration of the information available is underscored in order to overcome their inherent limitations.

Background— Growing evidence suggests that platelet reactivity (PR) may predict bleeding. We investigate the incremental value of PR in predicting bleeding after percutaneous coronary intervention (PCI) via the femoral approach over a validated bleeding risk score (BRS) of clinical and procedural variables. Methods and Results— A total of 800 patients undergoing elective PCI via the femoral approach were included. PR was measured before PCI with the VerifyNow P2Y12 assay and low PR was defined as a P2Y12 reaction unit value ≤178. Calculation of the BRS included the following: age, sex, intra-aortic balloon pump, glycoprotein IIb/IIIa inhibitors, chronic kidney disease, anemia, and low-molecular-weight heparin within 48-hour pre-PCI. A new risk score including low PR (BRS-PR) was developed and validated in an independent cohort of patients (n=310). Bleeding events at 30 days after PCI were defined according to the thrombolysis in myocardial infarction, Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE)-2, and Bleeding Academic Research Consortium criteria. Both BRS and PR showed high discriminatory power for bleeding (area under the curve [AUC] >0.7 for all definitions). Discriminatory power of BRS-PR (AUC=0.809 for thrombolysis in myocardial infarction bleeding; AUC=0.814 for Bleeding Academic Research Consortium class ≥2 bleeding; AUC=0.708 for Bleeding Academic Research Consortium class ≥3 bleeding; and AUC=0.813 for REPLACE-2 bleeding) was significantly higher than that of BRS alone ( P P =0.036). Conclusions— PR has incremental predictive value on bleeding events after elective PCI via the femoral approach over a validated risk score of clinical and procedural variables. A risk score including PR yields significantly better prognostic performance compared with the original BRS.

For accurate measurement of the fractional flow reserve (FFR) of the myocardium, the presence of maximum hyperemia is of paramount importance. It has been suggested that the hyperemic effect of the conventionally used hyperemic stimulus, adenosine, could be submaximal in patients who have microvascular dysfunction and that adding α-blocking agents could augment the hyperemic response in these patients. We studied the effect of the nonselective α-blocking agent phentolamine, which was administered in addition to adenosine after achieving hyperemia, in patients who had microvascular disease and those who did not. Thirty patients who were referred for percutaneous coronary intervention were selected. Of these 30 patients, 15 had strong indications for microvascular disease and 15 did not. FFR was measured using intracoronary adenosine, intravenous adenosine, and intracoronary papaverine before and after intracoronary administration of the nonselective α blocker phentolamine. In patients who did not have microvascular disease, no differences in hyperemic response to adenosine were noted, whether or not α blockade was given before adenosine administration; FFR levels before and after phentolamine were 0.76 and 0.75, respectively, using intracoronary adenosine (p = 0.10) and 0.75 and 0.74, respectively, using intravenous adenosine (p = 0.20). In contrast, in patients who had microvascular disease, some increase in hyperemic response was observed after administration of phentolamine; FFR levels decreased from 0.74 to 0.70 using intracoronary adenosine (p = 0.003) and from 0.75 to 0.72 using intravenous adenosine (p = 0.04). Although statistically significant, the observed further decrease in microvascular resistance after addition of phentolamine was small and did not affect clinical decision making in any patient. In conclusion, when measuring FFR, routinely adding an α-blocking agent to adenosine does not affect clinical decision making. © 2005 Elsevier Inc. All rights reserved.

We aimed to validate the technique of measuring the coronary flow reserve (CFR) with coronary pressure measurements against an established thermodilution technique. The CFR has traditionally required measurement of coronary blood flow velocity with the Doppler wire and, more recently, using a thermodilution technique with the coronary pressure wire. However, recent work has suggested that the CFR may be derived from pressure measurements alone (the ratio of the square root of the pressure drop across an epicardial stenosis during hyperemia to that value at rest). This depends on the assumption that friction losses across a coronary stenosis are negligible. We compared pressure-derived CFR values with those obtained by the thermodilution technique using the intracoronary pressure wire in 38 stenoses in 34 patients with significant coronary stenoses undergoing percutaneous intervention. We also compared these two techniques of measuring CFR in 25 stenoses (6 vessels) artificially created by inflating small balloons within a stented coronary artery after percutaneous intervention. There is a close linear relationship between pressure-derived and thermodilution CFR in native (r 2 = 0.52; p < 0.001) and artificial stenoses (r 2 = 0.54; p < 0.05), although the pressure-derived technique appears to systematically underestimate CFR values in both situations. This applies to native and artificial stenoses. Coronary flow reserve cannot be measured merely with pressure alone, and it cannot be safely assumed that friction losses are negligible across a native coronary stenosis. These data suggest that friction loss is an important determinant of the pressure gradient along an atherosclerotic coronary artery. © 2005 by the American College of Cardiology Foundation.

Background: Coronary flow reserve (CFR) and fractional flow reserve (FFR) provide complementary information on the coronary circulation. Using a pressure wire, it is possible to calculate CFR by thermodilution (CFRthermo), so that FFR and CFR can be measured with a single guide wire. The present multicentric study was performed to compare the feasibility of CFR thermo obtained with an improved algorithm and a standardized injection technique and its agreement with Doppler-derived CFR (CFR Doppler). Methods and results: In 86 patients with coronary artery disease recruited during 1 week in eight centres FFR, CFRthermo and CFRDoppler were measured. FFR could be obtained in all patients (100%). An optimal CFRDoppler could be obtained in 69% of the patients. CFRthermo could be obtained in 97% of the patients. A significant correlation was found between CFRDoppler and CFR thermo (r=0.79, Pthermo tended to be higher than CFRDoppler. Conclusions: In a setting close to 'real world' practice, this multicentric study confirms the feasibility and reliability of thermodilution-derived CFR. In addition, the safety and the swiftness of assessing FFR and CFR with one single guide wire makes the latter a unique clinical tool for the evaluation of the coronary circulation.

In this article, we provide very illustrative images obtained with optical coherence tomography (OCT) of a patient presenting with ST-elevation myocardial infarction and multivessel disease. These patients are referred to the catheterization laboratory without performing any prior noninvasive imaging. This leads very often to diagnostic dilemmas with difficult solutions. Coronary angiography is frequently insufficient or even misleading to guide the interventional cardiologist in the identification and revascularization of the culprit coronary lesion. What makes our case particularly paradigmatic is the fact that without OCT guidance, an erroneous clinical decision-making process would have taken place, leaving untreated the culprit lesion in this patient.

Age, creatinine, and ejection fraction (ACEF) score predict clinical outcomes in patients who underwent elective percutaneous coronary intervention (PCI) of nonocclusive coronary stenoses. We aimed at assessing the prognostic value of the ACEF score in patients who underwent successful PCI of chronic total occlusion (CTO). ACEF score was calculated in 587 patients treated with PCI of CTO: successful in 433 (74%; success group) and failed in 154 patients (26%; failure group). Patients were divided in ACEF tertiles: first0.950, second from 0.950 to 1.207, and third ACEF tertile1.207. Major adverse cardiac events (MACE = overall death + nonfatal myocardial infarction + clinically driven target vessel revascularization) were assessed in 558 patients (95%) up to 24 months (8 to 24 months). In success group, higher MACE rate was significantly associated with increasing ACEF tertile (first = 7%, second = 13%, third ACEF = 18%, p = 0.02). MACE-free survival was significantly decreased with increasing ACEF tertile (log-rank 5.58, p = 0.018). In the failure group, lower MACE rate was significantly associated with increasing ACEF tertile (p = 0.041). This was mainly driven by significant decreasing rate of target vessel revascularization along the tertiles (first = 34%, second = 19%, third ACEF = 10%, p = 0.007). Compared with success group, in failure group, MACE rate was significantly higher in the first tertile (p0.001) and similar in the third tertile (p = 0.59). In conclusion, ACEF score represents a simple tool in the prognostication of patients successfully treated with PCI of CTO and identifies those patients who would not derive any significant clinical harm despite failed percutaneous revascularization of the CTO.

We investigated the effect of β- and α-adrenergic blockers on fractional flow reserve (FFR) and index of microvascular resistance (IMR). In 43 patients (pts) with intermediate stenoses, we measured FFR and IMR before and after nonselective β-blocker propranolol (30 μg/kg, n = 20) and selective β1-blocker metoprolol (40 μg/kg, n = 23) IC; (b) In additional 21 pts after percutaneous coronary intervention (PCI), FFR and IMR were measured before and after α-blocker phentolamine (3 mg) IC. Neither propranolol nor metoprolol changed values of FFR and IMR. Phentolamine slightly decreased FFR (from 0.88 ± 0.05 to 0.87 ± 0.06, p = 0.025) but did not change IMR. FFR decreased from >0.80 to ≤0.80 in 3 pts (14%), but in none, the value decreased to

Patients with diabetes mellitus (DM) have increased baseline platelet reactivity and impaired response to antiplatelet drugs, compared to non-diabetics. Aim of the present study was to investigate whether thresholds for high platelet reactivity (HPR) that predict clinical outcomes after percutaneous coronary intervention (PCI) are similar in diabetic compared to non-diabetic patients. A total of 640 (32.6% with DM) consecutive patients taking aspirin and clopidogrel undergoing elective PCI were recruited. Platelet reactivity was measured immediately before the procedure with the VerifyNow P2Y12 assay. Primary end point was the 30-day incidence of major adverse cardiac events (MACE) in relation to the presence of DM and to P2Y12 reaction units (PRU) distribution. The optimal cut-off to predict 30-day MACE was a PRU value of256 in diabetics, and a PRU value of229 in non-diabetics. Accordingly, we redefined HPR on the basis of these two specific thresholds (HPR-ST), now including 60/209 (29%) diabetic patients with PRU256, and 130/431 (30%) non-diabetic patients with PRU229. HPR-ST discriminates significantly (p 0.001) patients with and without MACE, with a diagnostic accuracy of 73%. The combination of DM and HPR-ST resulted in the highest incidence of MACE (23.3%; p for trend0.001). At multivariate analysis, HPR-ST was the strongest independent predictor of 30-day MACE (odds ratio 4.80, 95% confidence interval 2.58-8.93; p 0.001). Redefining HPR based on specific thresholds for patients with and without DM significantly improves prediction of MACE post-PCI. Patients with HPR-ST, especially in the presence of DM, are at increased risk for ischemic events and may benefit from more aggressive antiplatelet strategies.